Use of a polyene macrolide antifungal agent in combination with a glycopeptide antibacterial agent

Abstract

This invention is directed to methods of administering a polyene macrolide antifungal agent in combination with a glycopeptide antibacterial agent having a substituent comprising at least about 8 carbon atoms. The invention is also directed to methods of using a polyene macrolide antifungal agent in combination with a specified glycopeptide antibacterial agent to treat fungal infections; and to compositions, kits and systems comprising a polyene macrolide antifungal agent and a specified glycopeptide antibacterial agent.

1. A method for treating a fungal infection in a subject, the method comprising:
 administering to the subject an antifungal amount of a polyene macrolide antifungal agent selected from amphotericin B or a pharmaceutically acceptable salt thereof; and a glycopeptide antibacterial agent of formula I: 
 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is —CH 2 CH 2 —NH—(CH 2 ) 9 CH 3  and R 7  is —CH 2 —NH—CH 2 —P(O)(OH) 2  or hydrogen; or R 1  is 4-(4-chlorophenyl)benzyl and R 7 is hydrogen; 
         or a pharmaceutically-acceptable salt thereof; 
         wherein the fungal infection is caused by  Candida albicans, Candida parapsilosis, Candida tropicalis, Candida krusei , or a combination thereof. 
       
     
     
       2. The method according to  claim 1 , wherein the polyene macrolide antifungal agent and the glycopeptide antibacterial agent are administered sequentially. 
     
     
       3. The method according to  claim 1 , wherein the polyene macrolide antifungal agent and the glycopeptide antibacterial agent are administered simultaneously. 
     
     
       4. A method for treating a fungal infection in a subject, the method comprising administering to the subject an antifungal amount of:
 (a) a polyene macrolide antifungal agent selected from amphotericin B, and nystatin; or a pharmaceutically acceptable salt thereof; and 
 (b) telavancin, or a pharmaceutically acceptable salt thereof; 
 wherein the fungal infection is caused by  Candida albicans, Candida parapsilosis, Candida tropicalis, Candida glabrata, Mucor circinelloides, Pseudallescheria boydii  or a combination thereof. 
 
     
     
       5. The method of  claim 4 , wherein the polyene macrolide antifungal agent is amphotericin B, or a pharmaceutically acceptable salt thereof. 
     
     
       6. A method for treating a fungal infection in a subject, the method comprising administering to the subject an antifungal amount of:
 (a) a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a polyene macrolide antifungal agent selected from amphotericin B, and nystatin; or a pharmaceutically acceptable salt thereof; and 
 (b) a pharmaceutical composition comprising a pharmaceutically acceptable carrier and telavancin or a pharmaceutically acceptable salt thereof; 
 wherein the fungal infection is caused by  Candida albicans, Candida parapsilosis, Candida tropicalis, Candida glabrata, Mucor circinelloides, Pseudallescheria boydii  or a combination thereof. 
 
     
     
       7. The method of  claim 6 , wherein the polyene macrolide antifungal agent is amphotericin B, or a pharmaceutically acceptable salt thereof. 
     
     
       8. A method for treating a fungal infection in a subject, the method comprising administering to the subject an antifungal amount of:
 (a) amphotericin B, or a pharmaceutically acceptable salt thereof; and 
 (b) telavancin, or a pharmaceutically acceptable salt thereof; 
 wherein the fungal infection is caused by  Candida albicans, Candida parapsilosis, Candida tropicalis, Candida krusei, Candida glabrata, Candida neoformans, Mucor circinelloides, Pseudallescheria boydii Aspergillus fumigatus, Rhizopus microsporus , or a combination thereof. 
 
     
     
       9. The method of  claim 7 , wherein the polyene macrolide antifungal agent is nystatin, or pharmaceutically acceptable salt thereof. 
     
     
       10. A method for treating a fungal infection in a subject, the method comprising administering to the subject an antifungal amount of:
 (a) amphotericin B, or a pharmaceutically acceptable salt thereof; and 
 (b) telavancin, or a pharmaceutically acceptable salt thereof; 
 wherein the fungal infection is caused by  Candida albicans, Candida parapsilosis, Candida tropicalis, Candida lcrusei, Candida glabrata, Candida neoformans, Mucor circinelloides, Pseudallescheria boydii, Aspergillus fumigatus, Rhizopus microsporus , or a combination thereof. 
 
     
     
       11. A method for treating a fungal infection in a subject, the method comprising administering to the subject an antifungal amount of:
 (a) nystatin, or a pharmaceutically acceptable salt thereof; and 
 (b) telavancin, or a pharmaceutically acceptable salt thereof; 
 wherein the fungal infection is caused by  Candida albicans, Candida parapsilosis, Candida tropicalis, Candida glabrata, Geotricium candidum, Mucor circinelloides, Pseudallescheria boydii , or a combination thereof.